Formation and stability of dispersed particles composed of vitamin K₁, soybean oil and phosphatidylcholine

Abstract

The purpose of this study was to develop an intravenous formulation composed of vitamin K₁ (VK) for the treatment of blood coagulation with warfarin-induced hypoprothrombinaemia. VK was dispersed using sonication with soybean phosphatidylcholine (PC) and the dispersion mechanism was evaluated by characterizing the dispersed particles with dynamic light scattering, fluorescence spectroscopy and surface monolayer techniques. VK has an appreciable solubility in PC bilayers (approximately 20 mol%). Within the VK molar fraction of 0.1–0.9, the size of the dispersed particles increased at room temperature within 3 months. By addition of soybean oil (SO) to VK (molar ratio of VK:SO=1:1), the solubility of the VK/SO mixtures in PC bilayers was decreased (approximately 5 mol%). The size of the aqueous dispersions at molar fractions of 0.1–0.7 was 50–70 nm and did not change for 3 months at room temperature. The solubility of the VK and VK/SO in PC bilayers is crucially important in the production of the stable aqueous dispersions of VK particles.